Id2a is required for hepatic outgrowth during liver development in zebrafish

Mech Dev. 2015 Nov;138 Pt 3:399-414. doi: 10.1016/j.mod.2015.05.001. Epub 2015 May 27.

Abstract

During development, inhibitor of DNA binding (Id) proteins, a subclass of the helix-loop-helix family of proteins, regulate cellular proliferation, differentiation, and apoptosis in various organs. However, a functional role of Id2a in liver development has not yet been reported. Here, using zebrafish as a model organism, we provide in vivo evidence that Id2a regulates hepatoblast proliferation and cell death during liver development. Initially, in the liver, id2a is expressed in hepatoblasts and after their differentiation, id2a expression is restricted to biliary epithelial cells. id2a knockdown in zebrafish embryos had no effect on hepatoblast specification or hepatocyte differentiation. However, liver size was greatly reduced in id2a morpholino-injected embryos, indicative of a hepatic outgrowth defect attributable to the significant decrease in proliferating hepatoblasts concomitant with the significant increase in hepatoblast cell death. Altogether, these data support the role of Id2a as an important regulator of hepatic outgrowth via modulation of hepatoblast proliferation and survival during liver development in zebrafish.

Keywords: Biliary epithelial cell; Differentiation; Helix-loop-helix; Hepatoblast; Inhibitor of DNA binding; Liver specification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bile Ducts, Intrahepatic / embryology
  • Cell Death
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Hepatocytes / cytology
  • In Situ Hybridization
  • Inhibitor of Differentiation Protein 2 / antagonists & inhibitors
  • Inhibitor of Differentiation Protein 2 / genetics
  • Inhibitor of Differentiation Protein 2 / physiology*
  • Liver / cytology
  • Liver / embryology*
  • Organogenesis / genetics
  • Organogenesis / physiology
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / physiology*
  • Zebrafish Proteins / antagonists & inhibitors
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology*

Substances

  • Id2a protein, zebrafish
  • Inhibitor of Differentiation Protein 2
  • Zebrafish Proteins